Identification of benzothiazinones containing 2-benzyl-2,7-diazaspiro[3.5]nonane moieties as new antitubercular agents.

Identification of benzothiazinones containing 2-benzyl-2,7-diazaspiro[3.5]nonane moieties as new antitubercular agents.
Eur J Med Chem. 2020 May 19;200:112409
Authors: Wang A, Ma C, Chai Y, Liu X, Lv K, Fu L, Wang B, Jia X, Liu M, Lu Y
Abstract
A series of new benzothiazinone derivatives containing a symmetric 2-benzyl-2,7-diazaspiro[3.5]nonane moiety, based on the structure of LK02 discovered in our lab, were designed and synthesized. With one exception 3, all of them show excellent in vitro activity against both drug-sensitive and clinically isolated multidrug-resistant Mycobacterium tuberculosis (MTB) strains (MIC: < 0.016 μg/mL). Compound 2d with a methyl group at the benzylic carbon, was identified to have good safety and significant efficacy in an acute mouse model of TB, as well as better PK profiles than PBTZ169.
PMID: 32460114 [PubMed - as supplied by publisher]

Source: European Journal of Medicinal Chemistry - May 18, 2020 Category: Chemistry Authors: Wang A, Ma C, Chai Y, Liu X, Lv K, Fu L, Wang B, Jia X, Liu M, Lu Y Tags: Eur J Med Chem Source Type: research